Amyloidogenesis in its biological environment: challenging a fundamental issue in protein misfolding diseases.
The inability of a protein to adopt its native and soluble conformation (protein misfolding) is the origin of an increasing number of human diseases. The misfolding of a protein is often associated with its assembly into extracellular fibrillar aggregates, commonly termed amyloid fibrils. Despite the many efforts expended to characterise amyloid formation in vitro, it is increasingly evident that the biological environment in which aggregation occurs naturally influences the mechanism and rate of the process, as well as the structure and stability of the resulting fibrils. This problem is not trivial because of the inherent complexity of biology and difficulty to design proper experiments able to address the molecular level of the phenomenon in vivo. We will show successful approaches that have been used recently and will illustrate some of the results that have contributed to elucidate important structural aspects of amyloid formation in vivo.
Bellotti
Vittorio
V
Dipartimento di Biochimica, Università di Pavia, Laboratori di Biotecnologie, IRCCS Policlinico San Matteo, via Taramelli 3b, I-27100 Pavia, Italy. vbellot@unipv.it
Chiti
Fabrizio
F
D000682:Amyloid / Q000737:chemistry* / Q000378:metabolism* / Q000648:ultrastructure; D000686:Amyloidosis / Q000378:metabolism* / Q000473:pathology; D000818:Animals; D006025:Glycosaminoglycans / Q000378:metabolism; D006801:Humans; D018625:Microscopy, Atomic Force; D008855:Microscopy, Electron, Scanning; D010829:Physiological Phenomena; D011487:Protein Conformation; D017510:Protein Folding; D011506:Proteins / Q000378:metabolism; D020543:Proteome / Q000032:analysis; D013499:Surface Properties
D000682:Amyloid; D006025:Glycosaminoglycans; D011506:Proteins; D020543:Proteome